scholarly journals Reduction in cisplatin genotoxicity (micronucleus formation) in non target cells of mice by protransfersome gel formulation used for management of cutaneous squamous cell carcinoma

2011 ◽  
Vol 61 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Vandana Gupta ◽  
Ramesh Agrawal ◽  
Piyush Trivedi

Reduction in cisplatin genotoxicity (micronucleus formation) in non target cells of mice by protransfersome gel formulation used for management of cutaneous squamous cell carcinomaCisplatin-loaded protransfersome system was prepared and characterized forin vitrodrug permeation, drug deposition and antitumor effect. A histopathological study and a genotoxicity study were also done. The skin permeation data of cisplatin from protransfersome gel formulation revealed 494.33 ± 11.87 μg cm-2, which was significantly higher than that from the control plain drug solution in 0.9 % NaCl (p< 0.001). Untreated group of animals showed invasive moderately differentiated keratinizing squamous cell carcinoma (malignant stage). However, with cisplatin loaded protransfersome gel system simple epithelial hyperplasia (pre-cancerous stage) with no cancerous growth was observed. Also, a significant induction in micronucleus formation was found in the group that was treated with injectable intraperitoneal cisplatin preparation in 0.9 % saline as compared to the group treated with topical protransfersome gel formulation. The findings of this research work appear to support improved, site-specific and localized drug action in the skin, thus providing a better option for dealing with skin related problems like squamous cell carcinoma.

2019 ◽  
Vol 20 (14) ◽  
pp. 3428 ◽  
Author(s):  
Sakinah Hassan ◽  
Karin J. Purdie ◽  
Jun Wang ◽  
Catherine A. Harwood ◽  
Charlotte M. Proby ◽  
...  

Background: Cutaneous squamous cell carcinoma (cSCC) incidence continues to rise with increasing morbidity and mortality, with limited treatment options for advanced disease. Future improvements in targeted therapy will rely on advances in genomic/transcriptomic understanding and the use of model systems for basic research. We describe here the panel of 16 primary and metastatic cSCC cell lines developed and characterised over the past three decades in our laboratory in order to provide such a resource for future preclinical research and drug screening. Methods: Primary keratinocytes were isolated from cSCC tumours and metastases, and cell lines were established. These were characterised using short tandem repeat (STR) profiling and genotyped by whole exome sequencing. Multiple in vitro assays were performed to document their morphology, growth characteristics, migration and invasion characteristics, and in vivo xenograft growth. Results: STR profiles of the cSCC lines allow the confirmation of their unique identity. Phylogenetic trees derived from exome sequence analysis of the matched primary and metastatic lines provide insight into the genetic basis of disease progression. The results of in vivo and in vitro analyses allow researchers to select suitable cell lines for specific experimentation. Conclusions: There are few well-characterised cSCC lines available for widespread preclinical experimentation and drug screening. The described cSCC cell line panel provides a critical tool for in vitro and in vivo experimentation.


2021 ◽  
Author(s):  
Lipeng Gao ◽  
Rong-Yin Gui ◽  
Xin-Nan Zheng ◽  
Ying-Xue Wang ◽  
Yao Gong ◽  
...  

Abstract Houttuynia cordata Thunb (HCT) is a medicinal and edible herb which has beneficial effects on various diseases due to its diuretic, anti-inflammatory, anti-oxidative, anti-microbial, anti-viral, anti-cancer and anti-diabetic properties. Most of reports of its anti-cancer activity were conducted in vitro, and its effects on cutaneous squamous cell carcinoma (SCC) has not been investigated yet. Using DMBA/TPA induced SCC mice model, we found that topical treatment by HCT, as well as its bioactive ingredient monomer, efficiently inhibited tumor growth. Mechanistically, we found tumor infiltrating CD4+, Foxp3+ T regulatory cells (Tregs) were significantly reduced and CD8+/Treg cells ratio was largely increased in tumors after HCT treatment. In addition, several chemokines which recruited immune cells were largely reduced when SCC cancer cells were treated by HCT in vitro. Our results demonstrate the therapeutic effects of HCT on cutaneous SCC and indicate it might inhibit cancer through regulating tumor infiltrating lymphocytes and the tumor immune microenvironments.


2014 ◽  
Vol 306 (5) ◽  
pp. 489-496 ◽  
Author(s):  
Dae-Kyoung Choi ◽  
Zheng Jun Li ◽  
In-Kyu Chang ◽  
Min-Kyung Yeo ◽  
Jin-Man Kim ◽  
...  

Oncogene ◽  
2021 ◽  
Author(s):  
Shukai Yuan ◽  
Peitao Zhang ◽  
Liqi Wen ◽  
Shikai Jia ◽  
Yufan Wu ◽  
...  

AbstractEmerging evidence suggests that the cancer stem cells (CSCs) are key culprits of cancer metastasis and drug resistance. Understanding mechanisms regulating the critical oncogenic pathways and CSCs function could reveal new diagnostic and therapeutic strategies. We now report that miR-22, a miRNA critical for hair follicle stem/progenitor cell differentiation, promotes tumor initiation, progression, and metastasis by maintaining Wnt/β-catenin signaling and CSCs function. Mechanistically, we find that miR-22 facilitates β-catenin stabilization through directly repressing citrullinase PAD2. Moreover, miR-22 also relieves DKK1-mediated repression of Wnt/β-catenin signaling by targeting a FosB-DDK1 transcriptional axis. miR-22 knockout mice showed attenuated Wnt/β-catenin activity and Lgr5+ CSCs penetrance, resulting in reduced occurrence, progression, and metastasis of chemically induced cutaneous squamous cell carcinoma (cSCC). Clinically, miR-22 is abundantly expressed in human cSCC. Its expression is even further elevated in the CSCs proportion, which negatively correlates with PAD2 and FosB expression. Inhibition of miR-22 markedly suppressed cSCC progression and increased chemotherapy sensitivity in vitro and in xenograft mice. Together, our results revealed a novel miR-22-WNT-CSCs regulatory mechanism in cSCC and highlight the important clinical application prospects of miR-22, a common target molecule for Wnt/β-catenin signaling and CSCs, for patient stratification and therapeutic intervention.


2021 ◽  
Vol 10 (5) ◽  
pp. 2219-2228
Author(s):  
Lipeng Gao ◽  
Tim Hua Wang ◽  
Champ Peng Chen ◽  
Jan Jian Xiang ◽  
Xu-Bo Zhao ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1993 ◽  
Author(s):  
Gabriella Pasqual-Melo ◽  
Thiago Nascimento ◽  
Larissa Juliani Sanches ◽  
Fernanda Paschoal Blegniski ◽  
Julya Karen Bianchi ◽  
...  

Cutaneous squamous cell carcinoma (SCC) is the most prevalent cancer worldwide, increasing the cost of healthcare services and with a high rate of morbidity. Its etiology is linked to chronic ultraviolet (UV) exposure that leads to malignant transformation of keratinocytes. Invasive growth and metastasis are severe consequences of this process. Therapy-resistant and highly aggressive SCC is frequently fatal, exemplifying the need for novel treatment strategies. Cold physical plasma is a partially ionized gas, expelling therapeutic doses of reactive oxygen and nitrogen species that were investigated for their anticancer capacity against SCC in vitro and SCC-like lesions in vivo. Using the kINPen argon plasma jet, a selective growth-reducing action of plasma treatment was identified in two SCC cell lines in 2D and 3D cultures. In vivo, plasma treatment limited the progression of UVB-induced SSC-like skin lesions and dermal degeneration without compromising lesional or non-lesional skin. In lesional tissue, this was associated with a decrease in cell proliferation and the antioxidant transcription factor Nrf2 following plasma treatment, while catalase expression was increased. Analysis of skin adjacent to the lesions and determination of global antioxidant parameters confirmed the local but not systemic action of the plasma anticancer therapy in vivo.


Nanomedicine ◽  
2019 ◽  
Vol 14 (15) ◽  
pp. 2027-2043 ◽  
Author(s):  
Lei Shi ◽  
Pei Liu ◽  
Jing Wu ◽  
Lun Ma ◽  
Han Zheng ◽  
...  

Aim: To clarify the effectiveness and safety of x-ray-activated photodynamic therapy (X-PDT) for cutaneous squamous cell carcinoma (SCC) and melanoma. Materials & methods: Copper-cysteamine nanoparticles were used as a photosensitizer of X-PDT. The dark toxicity and cytotoxicity were studied in vitro. Tumor volume, microvessel density and acute toxicity of mice were evaluated in vivo. Results: Without x-ray irradiation, copper-cysteamine nanoparticles were nontoxic for keratinocyte cells. XL50 cells (SCC) were more sensitive to X-PDT than B16F10 cells (melanoma). X-PDT successfully inhibited the growth of SCC in vivo (p < 0.05), while the B16F10 melanoma was resistant. Microvessel density in SCC tissue was remarkably reduced (p < 0.05). No obvious acute toxicity reaction was observed. Conclusion: X-PDT is a safe and effective treatment for SCC.


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